Non-Invasive Urinary Markers of Renal Dysfunction in Sickle Cell Disease.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4621-4621
Author(s):  
Davoud Mohtat ◽  
Thomas Moulton ◽  
M. Catherine Driscoll ◽  
Robert P Woroniecki
Keyword(s):  
Sickle Cell Disease ◽  
Renal Disease ◽  
Urinary Excretion ◽  
Sickle Cell ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Conflicts Of Interest ◽  
Enzyme Linked Immunosorbent Assay ◽  
Cell Disease ◽  
Tgf Β1

Abstract Abstract 4621 Renal failure is one of the major complications of sickle cell disease (SCD), affecting 5-18% of the patients. Microalbuminuria (MA), which has a prevalence of 26.5% in all children with SCD, is used as a marker of preclinical glomerular damage and renal disease progression. However, measuring MA alone may miss renal damage involving tubular proteins. We hypothesize that sickle cell nephropathy subjects will have increased urinary excretion of Transforming Growth Factor Beta-1 (TGF β1) and Neutrophil Gelatinase–Associated Lipocalin (NGAL) as compared to age-matched controls (CTR). We also hypothesize that urinary excretion of these proteins will be associated with severity of anemia in SCD. Enzyme-Linked Immunosorbent Assay (ELISA) kits were used to detect urinary excretion of TGF β1/NGAL, and corrected to urine creatinine. Mean age, gender, and race were not statistically different among the groups. Urinary excretion of TGF β1 was significantly higher in SCD subjects (26.4 pg/mg Cr +/-1.5) vs. CTR (14.9 pg/mg Cr +/-2.4), (p<0.00001). There was no difference in urinary NGAL between the SCD subjects vs. CTR. SCD patients with hemoglobin less than 9gm/dl had higher urinary TGF β1 than SCD patients with milder anemia (p=0.002). Urinary TGF β1 was lower in SCD patients on hydroxyurea (23.61+/-2.6), vs. those who were (27.69+/-1.8), p=0.08. Surprisingly, there were no correlation between urinary TGF β1 and urinary microalbumin or estimated glomerular function, indicating that microalbuminuria and serum creatinine are poor measures of renal injury in SCD patients. Our data suggests that urinary TGF β1 may serve as a urinary biomarker to monitor the progression of renal disease in SCD. This assumption needs to be tested prospectively. Disclosures: No relevant conflicts of interest to declare.

Urinary transforming growth factor beta-1 as a marker of renal dysfunction in sickle cell disease

2010 ◽  
Vol 26 (2) ◽  
pp. 275-280 ◽  
Author(s):  
Davoud Mohtat ◽  
Rosemary Thomas ◽  
Zangfang Du ◽  
Yaa Boakye ◽  
Thomas Moulton ◽  
...  
Keyword(s):  
Growth Factor ◽  
Sickle Cell Disease ◽  
Renal Dysfunction ◽  
Sickle Cell ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Cell Disease ◽  
Growth Factor Beta

Transient Elevations of Microalbuminuria May Represent a Marker of Systemic Vascular Injury in Sickle Cell Disease Patients.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4611-4611
Author(s):  
Borys Hrinczenko ◽  
Jeffrey R. Schelling
Keyword(s):  
Sickle Cell Disease ◽  
Renal Insufficiency ◽  
Renal Disease ◽  
Hospital Stay ◽  
Sickle Cell ◽  
Conflicts Of Interest ◽  
Response To Therapy ◽  
Cell Disease ◽  
Blood Disorder ◽  
Pain Crisis

Abstract Abstract 4611 Sickle cell disease (SCD) is a genetic blood disorder of hemoglobin function resulting in severe morbidity and early mortality. Hemolysis and vascular obstruction, endothelial activation and dysfunction, and inflammation, are hallmarks of this disease contributing to a chronic and progressive pathophysiology. Renal complications include hematuria, proteinuria, chronic renal insufficiency, and end stage renal disease. Several studies in SCD patients have shown that microalbuminuria may be a potential marker of progression to chronic renal disease. Also, microalbuminuria has been proposed as a marker of worsening outcome in diabetes, cardiovascular disease, cancer, lymphoma, and clotting. The Steno hypothesis (Diabetologia 1989; 32: 219) proposed that albuminuria is a biomarker of systemic vascular damage in diabetics, not just a marker of localized renal disease but also of retinopathy and macroangiopathy. We propose that the Steno hypothesis may also apply to SCD patients in that albuminuria may reflect systemic vascular disease injury besides potential renal impairment. From a cohort of 33 SCD patients in a county hospital hematology clinic, 11 patients were admitted through the emergency department with acute vaso-occlusive pain crisis over a one month period, and all were evaluated for microalbuminuria. [7 males, 4 females; 7 HbSS, 3 HbSC, 1 HbS beta-thalassemia; median age 41.7 years (range, 20 - 59 years), median hospital stay of 3.5 days (range, 2 – 8 days)]. None of the patients had renal insufficiency. Hospitalized patients were treated with intravenous fluids and intravenous narcotics. The median albuminuria value at admission was 21 mg/g creatinine. During hospitalization, 6 patients remained normoalbuminuric (<30 mg/g creatinine) during their entire hospital stay, 5 patients (3 HbSS, 2 HbSC) were microalbuminuric (30 – 299 mg/g creatinine), and none were macroalbuminuric (> 300 mg/g creatinine). Three of the microalbuminuric patients were followed with daily early morning albuminuria determinations. Two of those patients displayed a peak microalbuminuria level followed by a progressive drop at the time of hospital discharge. For instance, one HbSS patient was hospitalized for 8 days and at admission his albuminuria level was 69 mg/g creatinine. His daily microalbuminuria level progressively rose and peaked at 100 mg/g creatinine on hospital day 4, and then decreased daily to 86 mg/g creatinine at discharge on hospital day 8. Another microalbuminuric HbSC patient presented on admission with a microalbuminuria level of 67 mg/g creatinine. His microalbuminuria level peaked at 98 mg/g creatinine on hospital day 2 and then dropped to 3 mg/g creatinine at discharge on hospital day 4. These patients had elevations of their daily albuminuria values from initial baseline values during a pain crisis which peaked and then decreased as their crisis resolved and were discharged from the hospital. Only a subset of SCD patients hospitalized in pain crisis showed evanescent increases in albuminuria levels during a pain crisis. This incremental elevation of albuminuria represents an extension of the Steno hypothesis, in that it may serve as a sensitive biomarker for vaso-occlusive pain crisis, a unique form of systemic vascular endothelial injury. Furthermore, a decrease in microalbuminuria, or even a drop to normoalbuminuria, in SCD patients may be a useful marker to assess response to therapy. A prospective study on SCD patients with normoalbuminuria and microalbuminuria is needed to confirm this hypothesis. Disclosures: No relevant conflicts of interest to declare.

Chronobiology of Hypertension in Sickle Cell Disease

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4094-4094 ◽  
Author(s):  
Jeffrey D. Lebensburger ◽  
Daniel Feig ◽  
Lee Hilliard ◽  
David Askenazi ◽  
Thomas H. Howard ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Sickle Cell Disease ◽  
Renal Disease ◽  
Sickle Cell ◽  
Conflicts Of Interest ◽  
Laboratory Data ◽  
Clinic Visit ◽  
Cell Disease ◽  
Transfusion Therapy ◽  
Gold Standard Method

Abstract Introduction: Adult patients with Sickle Cell Disease (SCD): 1) develop renal failure at an earlier age than non-SCD black patients with end stage renal disease and 2) renal transplant outcomes in patients with SCD are so inferior that many transplant programs will not consider patients with SCD as candidates. More research is needed to understand the development of renal disease in patients with SCD; particularly in the earlier stages in which interventions might be most successful. In non-SCD pediatric populations, 24 hour Ambulatory Blood Pressure Monitoring (ABPM) is the gold standard method to document hypertension as it has been shown to be a better surrogate outcome for end organ damage from hypertension. The association between hypertension (as defined by ABPM) and progressive kidney disease needs to be assessed in SCD. Objective: To identify baseline blood pressure (BP) abnormalities as measured by ABPM and conventional clinic measurement and to characterize factors associated with ABPM abnormalities among a cohort of sickle cell participants enrolled in a 5 year prospective study of hypertension and progressive kidney injury. Methods: Participants ages 5-21 yrs with HbSS or SB0 thalassemia were enrolled in a five year IRB approved prospective cohort study; participants 11-20 yrs were also eligible to undergo 24 hr ABPM. Demographics, therapies,and laboratory data (CBC, CMP, uric acid, LDH, cystatin c, and urine microalbumin/creatinine) were recorded. The pre-transfusion CBC was used for patients on chronic transfusion therapy. Clinic BP and 24 hr ABPM (using SpaceLabs 90217 monitors which records BP every 20 minutes while awake and 30 minutes while asleep for at least 24 hours) were measured. BP level norms were determined by pediatric BP tables created by the NHLBI (clinic BP) and American Heart Association (ABPM) for age and height. Abnormal nocturnal dipping is defined as <10% BP dip (daytime-nighttime BP)/daytime BP x 100). Abnormal BP load is defined as > 25% of blood pressure recordings exceeding the 95th percentile BP for normative data. Results: At the time of this abstract, 29/108 (27%) of participants were hypertensive at their baseline clinic visit and 24-hr ABPM has been conducted in 27 participants (7 were normotensive in clinic; 20 were normotensive during clinic visit). Twenty two of the 27 (81%) participants were identified with abnormal systolic nocturnal BP dipping and 15/27 (56%) had abnormal diastolic nocturnal BP dipping. Of concern, 10/27 (37%) participants had an increase in SBP while sleeping and 7/27 (26%) had an increase in DBP while sleeping. Among the seven participants with hypertension in clinic, all had abnormal nocturnal BP dipping. In those participants with normal clinic BP, 15/20 (75%) had abnormal systolic BP dipping. Nine (33%) participants had an abnormal nocturnal systolic BP load and 7 (26%) participants had abnormal nocturnal diastolic BP load. Eight of 10 participants with an increase in systolic BP while sleeping were on chronic transfusion therapy (p=0.06). Variables that may be associated with an increase in systolic BP while sleeping were: lower GFR (p=0.06), higher BMI (p=0.02), and higher hemoglobin (p=0.08). Participants on chronic transfusion had a higher mean nocturnal systolic BP load than participants on no chronic therapy or hydroxyurea therapy (p=0.04). Variables that may be associated with an abnormal nocturnal systolic BP load were: lower GFR (p<0.001), higher BMI (p=0.01), and higher Hb (p=0.01). Transfusion volume (mL) was not associated with abnormal dipping (p=0.72) or BP load (p=0.52). Conclusion: Abnormal nocturnal BP is highly prevalent among SCD participants with and without hypertension in clinic. Blood therapy or need for blood therapy may be associated with abnormal nocturnal BP. Participants with abnormal nocturnal BP may have a lower GFR. Over time, this cohort will determine if abnormal nocturnal BP predicts a progressive decline in GFR in SCD as it does in non-SCD populations. Disclosures No relevant conflicts of interest to declare.

scholarly journals Vitamin D and Nonskeletal Complications among Egyptian Sickle Cell Disease Patients

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Mona Hamdy ◽  
Niveen Salama ◽  
Ghada Maher ◽  
Amira Elrefaee
Keyword(s):  
Vitamin D ◽  
Sickle Cell Disease ◽  
Vitamin D Deficiency ◽  
Sickle Cell ◽  
Standard Of Care ◽  
Enzyme Linked Immunosorbent Assay ◽  
Cell Disease ◽  
P Values ◽  
Indirect Bilirubin ◽  
Deficient Group

Lower levels of vitamin D have been documented in many patients with sickle cell disease (SCD), but data are still inconclusive regarding the association between vitamin D deficiency (VDD) and the occurrence or the severity of various SCD complications. Our study aimed to detect the prevalence of vitamin D deficiency among Egyptian patients with SCD and to associate it with the clinical course of the disease. We measured the level of 25-hydroxy vitamin D in 140 children (age from 4.3 to 15.5years), 80 patients with SCD and 60 controls using enzyme-linked immunosorbent assay. Vitamin D was deficient in 60% of SCD compared to 26.7% of controls. Severe VDD was significantly higher in SCD patients than controls. Patients were divided into 2 groups; Normal group (32 patients) and Deficient group (48 patients). There were statistically significant differences between the 2 groups regarding their age, height percentile, the presence of clinical jaundice, and osseous changes (P values 0.043, 0.024, 0.001, and 0.015, respectively). Hemoglobin and hematocrit values were significantly lower in Deficient group (P values 0.022 and 0.004, respectively) while the levels of aspartate aminotransferase, lactate dehydrogenase, and total and indirect bilirubin were significantly higher in the same group (P values 0.006, 0.001, 0.038, and 0.016, respectively). The frequency of blood transfusions, hospitalization, and vasoocclusive crisis previous year as well as the history of bone fracture and recurrent infections proved to be significantly higher in Deficient group. These findings suggest that VDD may play a role in the pathogenesis of hemolysis and other complication of SCD. Vitamin D monitoring and supplementation in patients with SCD should be implemented as a standard of care to potentially improve health outcomes in these affected patients.

scholarly journals Associations between TGF-β1 Levels and Markers of Hemolysis, Inflammation, and Tissue Remodeling in Pediatric Sickle Cell Patients

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Rayra P. Santiago ◽  
Magda O. S. Carvalho ◽  
Camylla V. B. Figueiredo ◽  
Luciana M. Fiuza ◽  
Rodrigo M. Oliveira ◽  
...  
Keyword(s):  
Sickle Cell ◽  
Transforming Growth Factor Beta ◽  
Pediatric Patients ◽  
Transforming Growth Factor ◽  
Vascular Dysfunction ◽  
Healthy Control ◽  
Biochemical Analyses ◽  
Laboratory Biomarkers ◽  
Metalloproteinase 9 ◽  
Tgf Β1

Transforming growth factor beta (TGF-β) is a cytokine with important involvement in biological processes related to the pathogenesis of sickle cell disease (SCD), including endothelial and vascular dysfunction, inflammation, and hematopoietic homeostasis. This study is aimed at investigating associations between levels of TGF-β1 and classical laboratory biomarkers and inflammatory mediators, as well as the tissue inhibitor of metalloproteases-1 (TIMP-1) and matrix metalloproteinase-9 (MMP-9), in pediatric patients ( n = 123 ) with SCD in steady state: 84 with sickle cell anemia (HbSS) and 39 with hemoglobin SC disease (HbSC). A healthy control (HC) group of 59 individuals was also included. Hematological and biochemical analyses were carried out using electronic methods. TGF-β1, TIMP-1, and MMP-9 plasma quantifications were performed by ELISA. TGF-β1 plasma levels were higher in HbSS individuals than in HbSC and HC. In individuals with HbSS, TGF-β1 levels were positively correlated with red blood cells, hemoglobin, hematocrit, platelets, and TIMP-1. In addition, HbSS individuals with TGF-β1 levels above the median (≥72.29 ng/mL) also presented increased monocyte counts and decreased albumin levels. In patients with HbSC, TGF-β1 levels were positively correlated with leukocytes, eosinophils, lymphocytes, monocytes, and platelets, as well as levels of TIMP-1, VLDL-C, triglycerides, heme, and AST. Additionally, HbSC individuals with TGF-β1 levels above the median (≥47.80 ng/mL) presented increased leukocyte and platelet counts, as well as increased levels of triglycerides, VLDL-C, MMP-9, and TIMP-1, and decreased HDL-C. Our findings suggest that TGF-β1 may play important roles in vascular remodeling, vasculopathy, angiogenesis, and inflammation in pediatric patients with SCD.

scholarly journals Case Report: Acute Stroke in Young Adult Patient with Moyamoya Syndrome Secondary to Sickle Cell Disease

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 13-13
Author(s):  
Oladipo Cole ◽  
Asia Filatov ◽  
Javed Khanni ◽  
Patricio Espinosa
Keyword(s):  
Case Report ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Moyamoya Disease ◽  
Conflicts Of Interest ◽  
Acute Chest Syndrome ◽  
African American Female ◽  
Moyamoya Syndrome ◽  
Cell Disease ◽  
Radiographic Findings

Moyamoya disease, well described in literature, is a chronic cerebrovascular occlusive disorder. It is characterized by progressive stenosis/occlusion of the terminal portions of the internal carotid arteries (ICA) and the proximal portions of the middle cerebral arteries (MCA). Less frequently described is Moyamoya syndrome, the name given to radiographic findings consistent with Moyamoya disease, but with an identifiable cause. The diseases associated with Moyamoya Syndrome include Sickle Cell Disease (SCD), Thalassemias, and Down's Syndrome to name a few. Common complications of Moyamoya include both ischemic and hemorrhagic strokes. Upon literature review, Moyamoya syndrome caused by SCD is not well described. When it is, the discussion is centered around the pediatric patient population and surgical management. Our case report describes a 22-year-old African American female with SCD who initially presented with Acute Chest Syndrome. Her hospital course was complicated by development of overt debilitating neurologic deficits. Subsequently, she was found to have Moyamoya Syndrome on neuroimaging. She was successfully treated with medical management without any surgical intervention. This case highlights the necessity of thorough examination, differential diagnosis, imaging findings, and consideration of predisposing syndromes in the work-up for Moyamoya syndrome; especially individuals with Sickle Cell Disease. Disclosures No relevant conflicts of interest to declare.

scholarly journals Utility of Procalcitonin in Differentiating Acute Chest Syndrome from Vaso-Occlusive Crisis in Sickle Cell Disease

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 10-11
Author(s):  
Satish Maharaj ◽  
Simone Chang ◽  
Karan Seegobin ◽  
Marwan Shaikh ◽  
Kamila I. Cisak
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Complete Blood Count ◽  
Conflicts Of Interest ◽  
Statistical Significance ◽  
Acute Chest Syndrome ◽  
Adult Males ◽  
Cell Disease ◽  
Unequal Variances ◽  
Recorded Data

Background: Acute chest syndrome (ACS) frequently complicates sickle cell disease (SCD) and is a leading cause of hospitalization and mortality. Many factors have been implicated in ACS, including infections, thrombosis, fat and pulmonary emboli. However, a clear etiology is not defined in 50% of the cases and ACS is considered a clinical endpoint for different pathogenic processes (Vichinsky et al 2000). The non-specific nature of ACS makes diagnostic tests challenging, and there are no serum tests clinical used to aid diagnosis. Procalcitonin (PCT) is a prohormone of calcitonin and serum PCT rises within hours of an inflammatory stimulus. PCT has clinical utility as a marker of severe systemic inflammation, infection, and sepsis (Becker et al. 2008). Few studies have evaluated PCT as a biomarker for ACS in patients presenting with vaso-occlusive crises (VOC). Two studies have reported no difference in PCT (Biemond et al. 2018 and Stankovic et al 2011), while one study reported higher PCT between ACS and VOC (Patel et al 2014). Methods: We retrospectively reviewed 106 patients with SCD who presented to the emergency department with fever and painful crises during 2015-2019. The patients were divided into two categories based on discharge diagnoses - patients with VOC only (n=88) and patients with ACS (n=18). Inclusion criteria for both groups were patients with SCD, 17 years and older and PCT measurement on presentation. Exclusion criteria were defined as patients who had received empiric antibiotics prior to PCT testing. Data collected on presentation included genotype, age, gender, complete blood count, PCT, creatinine, total bilirubin and hydroxyurea use. Length of stay was recorded. Data was analyzed between the two groups using descriptive statistics and accounting for unequal variances, withp-value set at 0.05 for significance. Results: Demographics and clinical characteristics are summarized in Table 1 (Figure). The sample included primarily adult males (77%), with about two-thirds on hydroxyurea. Genotype HbSS (73.6%) was most prevalent followed by HbSC (22.6%) and HbSβ (3.8%). The ACS group had a higher percentage of HbSS, lower use of hydroxyurea and higher mean bilirubin. Mean PCT for the ACS group was 0.52 ng/mL (range, 0.05-2.04), compared to 0.31 ng/mL (range, 0.02-6.82) in the VOC group; withp=0.084. ROC analysis showed a PCT&gt;0.5ng/mL had 39% sensitivity and 85% specificity for ACS in this sample. Conclusion: In this sample, PCT on presentation was higher in those with ACS compared to VOC, but this difference did not achieve statistical significance. Further study in a larger population would be useful to evaluate this finding. Disclosures No relevant conflicts of interest to declare.

scholarly journals Interferon Induction By HbS, SERINC5 Upregulation and Reduction of HIV-1 Nef and AP2 Contribute to HIV-1 Restriction in Sickle Cell Disease

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 5-6
Author(s):  
Namita Kumari ◽  
Marina Jerebtsova ◽  
Songping Wang ◽  
Sharmin Diaz ◽  
Sergei Nekhai
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Mononuclear Cells ◽  
Conflicts Of Interest ◽  
Ex Vivo ◽  
Interferon Response ◽  
Cell Disease ◽  
Restriction Factors ◽  
Peripheral Blood Mononuclear ◽  
Hiv 1

Concerted action of numerous positively acting cellular factors is essential for Human immunodeficiency virus type 1 (HIV-1) replication but in turn is challenged by anti-viral restriction factors. Previously we showed that ex vivo one round HIV-1 replication and replication of fully competent T-tropic HIV-1(IIIB) is significantly reduced in peripheral blood mononuclear cells (PBMCs) obtained from patients with Sickle Cell Disease (SCD). Further, we identified and confirmed CDKN1A (p21) and CH25H as host restriction factors expressed in SCD PBMCs that may contribute to the HIV-1 inhibition, in addition to the previously reported SAMHD1 and IKBα. Since CH25H is an interferon stimulated gene (ISG), we analyzed IRFs and interferon expression in SCD PBMCs. Higher levels of IRF7 and IFNβ mRNA were observed in SCD PBMCs compared to controls. We probed further to ascertain if hemin or sickle Hb was responsible for interferon response. We found upregulation of IFNβ in THP-1 - derived macrophages treated with lysates of HbSS RBCs or purified HbS as compared to untreated or HbA treated controls. HbSS RBCs lysates and purified HbS inhibited HIV-1 gag mRNA expression in monocyte-derived macrophages infected with HIV-1(Ba-L). Recent clinical study showed increased levels of CD4 in HIV-1 infected SCD patients in Africa. Thus we analyzed CD4 levels in HIV-1 IIIB infected SCD PBMCs, and found them to be higher compared to controls. Levels of HIV-1 nef mRNA, that controls CD4 expression was lower in HIV-1 IIIB infected SCD PBMCs. As Nef counteracts SERINC3/5 restriction factor, we analyzed its expression as well as the expression of AP2 clathrin adaptor that is required for Nef mediated internalization of CD4. AP2 expression was lower and SERINC5 expression was higher in SCD PBMCs. CONCLUSIONS: SCD PBMCs could resist HIV-1 infection because of the increased IFNβ production by macrophages exposed to HbSS or sickle cell RBCs. SCD PBMC have increased levels of SERNIC5 and lower levels of HIV-1 Nef and host AP2 expression that, culumlatively, can increased CD4 levels and lead to the overall improved immunological health of SCD patients. ACKNOWLEDGMENTS: This work was supported by NIH Research Grants (1P50HL118006, 1R01HL125005, 1SC1HL150685, 5U54MD007597, 1UM1AI26617 and P30AI087714). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Disclosures No relevant conflicts of interest to declare.

scholarly journals American Society of Hematology 2020 guidelines for sickle cell disease: transfusion support

2020 ◽  
Vol 4 (2) ◽  
pp. 327-355 ◽  
Author(s):  
Stella T. Chou ◽  
Mouaz Alsawas ◽  
Ross M. Fasano ◽  
Joshua J. Field ◽  
Jeanne E. Hendrickson ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Iron Overload ◽  
Sickle Cell ◽  
Conflicts Of Interest ◽  
Guideline Development ◽  
Practice Research ◽  
Evidence Based ◽  
Red Cell ◽  
Cell Disease ◽  
American Society

Background: Red cell transfusions remain a mainstay of therapy for patients with sickle cell disease (SCD), but pose significant clinical challenges. Guidance for specific indications and administration of transfusion, as well as screening, prevention, and management of alloimmunization, delayed hemolytic transfusion reactions (DHTRs), and iron overload may improve outcomes. Objective: Our objective was to develop evidence-based guidelines to support patients, clinicians, and other healthcare professionals in their decisions about transfusion support for SCD and the management of transfusion-related complications. Methods: The American Society of Hematology formed a multidisciplinary panel that was balanced to minimize bias from conflicts of interest and that included a patient representative. The panel prioritized clinical questions and outcomes. The Mayo Clinic Evidence-Based Practice Research Program supported the guideline development process. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to form recommendations, which were subject to public comment. Results: The panel developed 10 recommendations focused on red cell antigen typing and matching, indications, and mode of administration (simple vs red cell exchange), as well as screening, prevention, and management of alloimmunization, DHTRs, and iron overload. Conclusions: The majority of panel recommendations were conditional due to the paucity of direct, high-certainty evidence for outcomes of interest. Research priorities were identified, including prospective studies to understand the role of serologic vs genotypic red cell matching, the mechanism of HTRs resulting from specific alloantigens to inform therapy, the role and timing of regular transfusions during pregnancy for women, and the optimal treatment of transfusional iron overload in SCD.

scholarly journals Hemoglobin-Specific Antibody in a Multiply Transfused Patient With Sickle Cell Disease

Blood ◽  
1997 ◽  
Vol 89 (6) ◽  
pp. 2155-2158 ◽  
Author(s):  
Peter A. Noronha ◽  
Loyda N. Vida ◽  
C. Lucy Park ◽  
George R. Honig
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Solid Phase ◽  
Enzyme Linked Immunosorbent Assay ◽  
Antibody Activity ◽  
Cell Disease ◽  
Serum Samples ◽  
Igg Antibody ◽  
Microtiter Plates ◽  
Level Of Activity

Abstract Human hemoglobins (Hbs) are known to be immunogenic, and both normal and variant forms of Hb have been shown to stimulate antibody formation in a variety of animal species. In patients who are homozygous for the sickle Hb (HbS) mutation, transfusion of normal, HbA-containing erythrocytes provides a potential stimulus for HbA alloimmunization. We tested serum samples for the presence of anti-Hb antibody by a solid-phase enzyme-linked immunosorbent assay (ELISA) using Hb-coated polystyrene microtiter plates. Hb-bound antibody was identified using an antihuman IgG antibody. Serum samples from 89 patients with sickle cell disease were initially tested for evidence of Hb antibody. The serum from three individuals exhibited antibody activity against HbA with little or no activity against HbS. Only one of them, a multiply transfused adult with HbSS, was available for further study. When this patient's antibody was tested against a variety of normal and mutant Hbs using antibody either to human IgG or to κ chains, the anti-Hb antibody demonstrated specificity for the region of the Hb β chain corresponding to the site of the amino acid substitution of HbS. The level of activity of the patient's anti-HbA showed no significant change over 1.5 years of observation. The transfusion of erythrocytes containing Hb structurally different from that of the recipient appeared to be capable of stimulating the production of Hb-specific alloimmune antibody.

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